Tailoring a Plasmodium vivax Vaccine To Enhance Efficacy through a Combination of a CSP Virus-Like Particle and TRAP Viral Vectors.
Tailoring a Plasmodium vivax Vaccine To Enhance Efficacy through a Combination of a CSP Virus-Like Particle and TRAP Viral Vectors.
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DOI：
10.1128/iai.00114-18
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发表时间：
2018-09
影响因子：
3.1
通讯作者：
Reyes-Sandoval A
中科院分区：
文献类型：
--
作者：
Atcheson E;Bauza K;Salman AM;Alves E;Blight J;Viveros-Sandoval ME;Janse CJ;Khan SM;Hill AVS;Reyes-Sandoval A
间日疟疾仍然是最严重和最被忽视的热带病之一，每年有1.32亿至3.91亿临床病例，有25亿人面临感染风险。针对间日疟原虫的疫苗可能比任何其他干预措施产生更大的影响，并且使用针对多种抗原的疫苗可能比针对单一抗原的疫苗对孢子虫感染产生更高的效力。间日疟疾仍然是最严重和最被忽视的热带病之一，每年有1.32亿至3.91亿临床病例，有25亿人面临感染风险。针对间日疟原虫的疫苗可能比任何其他干预措施产生更大的影响，并且使用针对多种抗原的疫苗可能比针对单一抗原的疫苗对孢子虫感染产生更高的效力。在这里，两种主要的间日疟原虫红细胞前疫苗候选抗原，间日疟原虫环孢子子蛋白（PvCSP）和血小板应答蛋白相关粘附蛋白（PvTRAP）作为联合疫苗递送。该策略提供了剂量节约效应，在小鼠中使用单独提供低保护或无保护的剂量，如未佐剂抗原PvTRAP（0%）和PvCSP(50%)，达到100%的无菌保护，并达到与佐剂成分相似的保护。采用一种新的小鼠攻毒模型来评估抗疟疾感染的效果，该模型由同时表达PvCSP和PvTRAP的双转基因伯氏疟原虫组成，该模型用病毒样颗粒（VLP） Rv21免疫小鼠，而PvTRAP同时用于黑猩猩腺病毒和修饰的牛痘病毒安卡拉（MVA）载体（病毒载体TRAP），此前报道使用Matrix-M佐剂在小鼠中诱导高效。或vvTRAP)来支持T细胞的有效诱导。我们在批准用于人的两种佐剂（AddaVax和Matrix-M）的背景下检测了这些疫苗引起的免疫。与Rv21结合使用时，Matrix-M支持最高的抗PvCSP抗体滴度，有趣的是，混合PvCSP、Rv21和PvTRAP病毒载体比单一疫苗提供的水平更能增强对疟疾的免疫力。
Vivax malaria remains one of the most serious and neglected tropical diseases, with 132 to 391 million clinical cases per year and 2.5 billion people at risk of infection. A vaccine against Plasmodium vivax could have more impact than any other intervention, and the use of a vaccine targeting multiple antigens may result in higher efficacy against sporozoite infection than targeting a single antigen. Vivax malaria remains one of the most serious and neglected tropical diseases, with 132 to 391 million clinical cases per year and 2.5 billion people at risk of infection. A vaccine against Plasmodium vivax could have more impact than any other intervention, and the use of a vaccine targeting multiple antigens may result in higher efficacy against sporozoite infection than targeting a single antigen. Here, two leading P. vivax preerythrocytic vaccine candidate antigens, the P. vivax circumsporozoite protein (PvCSP) and the thrombospondin-related adhesion protein (PvTRAP) were delivered as a combined vaccine. This strategy provided a dose-sparing effect, with 100% sterile protection in mice using doses that individually conferred low or no protection, as with the unadjuvanted antigens PvTRAP (0%) and PvCSP (50%), and reached protection similar to that of adjuvanted components. Efficacy against malaria infection was assessed using a new mouse challenge model consisting of a double-transgenic Plasmodium berghei parasite simultaneously expressing PvCSP and PvTRAP used in mice immunized with the virus-like particle (VLP) Rv21 previously reported to induce high efficacy in mice using Matrix-M adjuvant, while PvTRAP was concomitantly administered in chimpanzee adenovirus and modified vaccinia virus Ankara (MVA) vectors (viral-vectored TRAP, or vvTRAP) to support effective induction of T cells. We examined immunity elicited by these vaccines in the context of two adjuvants approved for human use (AddaVax and Matrix-M). Matrix-M supported the highest anti-PvCSP antibody titers when combined with Rv21, and, interestingly, mixing PvCSP Rv21 and PvTRAP viral vectors enhanced immunity to malaria over levels provided by single vaccines.